The penetrative ability of X-rays makes them valuable for structural imaging applications ranging from medical imaging and materials research to quality control and security. Transmission imaging with X-rays is typically used to produce an attenuation contrast image of the material of interest. However, these images suffer from poor contrast sensitivity that poses severe limitations in many applications. X-ray systems that employ photon counting detectors provide a number of advantages over older X-ray technologies that employ energy integrating detectors. For example, using a photon counting detector applying multiple detector energy thresholds, multiple contrast media can be simultaneously imaged and are distinguishable. Accordingly, X-ray systems using photon counting detectors show promise in a variety of innovative clinical applications.